PUBLICATION

Retinoic acid and Cyp26b1 are critical regulators of osteogenesis in the axial skeleton

Authors

Spoorendonk, K.M., Peterson-Maduro, J., Renn, J., Trowe, T., Kranenbarg, S., Winkler, C., and Schulte-Merker, S.

ID

ZDB-PUB-081022-34

Date

2008

Source

Development (Cambridge, England) 135(22): 3765-3774 (Journal)

Registered Authors

Peterson-Maduroe, Josi, Renn, Joerg, Schulte-Merker, Stefan, Spoorendonk, Kirsten, Trowe, Torsten, Winkler, Christoph

Keywords

Cyp26b1, Osteoblast, Osteogenesis, Retinoic acid, Zebrafish

MeSH Terms

Tretinoin/pharmacology*
Gene Expression Regulation, Developmental
Animals
Embryo, Nonmammalian/cytology
Embryo, Nonmammalian/embryology
Embryo, Nonmammalian/metabolism
Oryzias
Osteoblasts/cytology
Osteoblasts/drug effects
Osteoblasts/enzymology
Transcription Factors/genetics
Transcription Factors/metabolism
Osteogenesis*/drug effects
Phenotype
Zebrafish/embryology
Zebrafish/metabolism
Mice
Animals, Genetically Modified
Cytochrome P-450 Enzyme System/metabolism*
Mutation/genetics
Gene Expression Regulation, Enzymologic

(all 21)

PubMed

18927155 Full text @ Development

Abstract

Retinoic acid (RA) plays important roles in diverse biological processes ranging from germ cell specification to limb patterning. RA ultimately exerts its effect in the nucleus, but how RA levels are being generated and maintained locally is less clear. Here, we have analyzed the zebrafish stocksteif mutant, which exhibits severe over-ossification of the entire vertebral column. stocksteif encodes cyp26b1, a cytochrome P450 member that metabolizes RA. The mutant is completely phenocopied by treating 4 dpf wild-type embryos with either RA or the pharmacological Cyp26 blocker R115866, thus identifying a previously unappreciated role for RA and cyp26b1 in osteogenesis of the vertebral column. Cyp26b1 is expressed within osteoblast cells, demonstrating that RA levels within these cells need to be tightly controlled. Furthermore, we have examined the effect of RA on osteoblasts in vivo. As numbers of osteoblasts do not change upon RA treatment, we suggest that RA causes increased activity of axial osteoblasts, ultimately resulting in defective skeletogenesis.

Genes / Markers

Marker	Marker Type	Name
col10a1a	GENE	collagen, type X, alpha 1a
cyp26b1	GENE	cytochrome P450, family 26, subfamily b, polypeptide 1
sp7	GENE	Sp7 transcription factor
twist2	GENE	twist2

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
col10a1a	cyp26b1^sa2/sa2	standard conditions	Day 4	cleithrum	ISH	Fig. 2
col10a1a	cyp26b1^sa2/sa2	standard conditions	Day 4	entopterygoid	ISH	Fig. 2
col10a1a	cyp26b1^sa2/sa2	standard conditions	Day 4	opercle	ISH	Fig. 2
col10a1a	cyp26b1^sa2/sa2	standard conditions	Day 4	parasphenoid	ISH	Fig. 2
col10a1a	WT	standard conditions	Day 4	cleithrum	ISH	Fig. 2
col10a1a	WT	standard conditions	Day 4	entopterygoid	ISH	Fig. 2
col10a1a	WT	standard conditions	Day 4	opercle	ISH	Fig. 2
col10a1a	WT	standard conditions	Day 4	parasphenoid	ISH	Fig. 2
cyp26b1	cyp26b1^sa2/sa2	standard conditions	Day 6	cleithrum	ISH	Fig. S4
cyp26b1	cyp26b1^sa2/sa2	standard conditions	Day 6	hindbrain	ISH	Fig. S4

1 - 10 of 45

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
cyp26b1^sa2/+; cyp26b1^sa3/+	standard conditions	Days 7-13	basihyal cartilage malformed, abnormal	Fig. 2
cyp26b1^sa2/+; cyp26b1^sa3/+	standard conditions	Days 7-13	ceratohyal cartilage malformed, abnormal	Fig. 2
cyp26b1^sa2/+; cyp26b1^sa3/+	standard conditions	Days 7-13	ethmoid cartilage malformed, abnormal	Fig. 2
cyp26b1^sa2/sa2	standard conditions	Days 7-13	ceratohyal cartilage malformed, abnormal	Fig. 2
cyp26b1^sa2/sa2	standard conditions	Days 7-13	ethmoid cartilage decreased size, abnormal	Fig. 2
cyp26b1^sa2/sa2	standard conditions	Days 7-13	ethmoid cartilage malformed, abnormal	Fig. 2
cyp26b1^{t24295/t24295}	standard conditions	Days 7-13	ceratohyal cartilage malformed, abnormal	Fig. 2
cyp26b1^{t24295/t24295}	standard conditions	Days 7-13	regulation of ossification disrupted, abnormal	Fig. 1
cyp26b1^{t24295/t24295}	standard conditions	Days 7-13	vertebra fused with vertebra, abnormal	Fig. 1
cyp26b1^{t24295/t24295}	standard conditions	Days 7-13	vertebra malformed, abnormal	Fig. 1

1 - 10 of 16

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
sa2		Point Mutation	cyp26b1
sa3		Point Mutation	cyp26b1
t24295		Unknown	cyp26b1
zf131Tg	Tg1(Ola.Sp7:mCherry)	Transgenic Insertion
zf132Tg	Tg(Ola.Sp7:NLS-GFP)	Transgenic Insertion

1 - 5 of 5

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Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
cyp26b1^sa2/sa2
cyp26b1^sa2/+; cyp26b1^sa3/+
cyp26b1^{t24295/t24295}
WT
zf131Tg
zf132Tg

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP
mCherry	EFG	mCherry

Mapping

Entity Type	Entity Symbol	Location
BAC	CH211-197C14	Chr: 7 Details
Feature	t24295	Chr: 7 Details
GENE	cyp26b1	Chr: 7 Details

Spoorendonk et al., 2008 ZDB-PUB-081022-34 PMID:18927155

Retinoic acid and Cyp26b1 are critical regulators of osteogenesis in the axial skeleton

Spoorendonk et al., 2008

ZDB-PUB-081022-34
PMID:18927155